S4MPLE—Sampler for Multiple Protein-Ligand Entities: Methodology and Rigid-Site Docking Benchmarking
AbstractThis paper describes the development of the unified conformational sampling and docking tool called Sampler for Multiple Protein-Ligand Entities (S4MPLE). The main novelty in S4MPLE is the unified dealing with intra- and intermolecular degrees of freedom (DoF). While classically programs are either designed for folding or docking, S4MPLE transcends this artificial specialization. It supports folding, docking of a flexible ligand into a flexible site and simultaneous docking of several ligands. The trick behind it is the formal assimilation of inter-molecular to intra-molecular DoF associated to putative inter-molecular contact axes. This is implemented within the genetic operators powering a Lamarckian Genetic Algorithm (GA). Further novelty includes differentiable interaction fingerprints to control population diversity, and fitting a simple continuum solvent model and favorable contact bonus terms to the AMBER/GAFF force field. Novel applications—docking of fragment-like compounds, simultaneous docking of multiple ligands, including free crystallographic waters—were published elsewhere. This paper discusses: (a) methodology, (b) set-up of the force field energy functions and (c) their validation in classical redocking tests. More than 80% success in redocking was achieved (RMSD of top-ranked pose < 2.0 Å). View Full-Text
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Hoffer, L.; Chira, C.; Marcou, G.; Varnek, A.; Horvath, D. S4MPLE—Sampler for Multiple Protein-Ligand Entities: Methodology and Rigid-Site Docking Benchmarking. Molecules 2015, 20, 8997-9028.
Hoffer L, Chira C, Marcou G, Varnek A, Horvath D. S4MPLE—Sampler for Multiple Protein-Ligand Entities: Methodology and Rigid-Site Docking Benchmarking. Molecules. 2015; 20(5):8997-9028.Chicago/Turabian Style
Hoffer, Laurent; Chira, Camelia; Marcou, Gilles; Varnek, Alexandre; Horvath, Dragos. 2015. "S4MPLE—Sampler for Multiple Protein-Ligand Entities: Methodology and Rigid-Site Docking Benchmarking." Molecules 20, no. 5: 8997-9028.